R. Tyagi and M. N. Gupta*

Received July 2, 1997
The protein function as well as its stability is governed by the amino
acid sequence which in turn defines the collective noncovalent
interactions leading to its specific conformation. Hence, it is not
surprising that chemical modification with monofunctional and
bifunctional reagents (the latter is called chemical cross-linking)
causes structural changes (sometimes even subtle) which can result in
significant changes in the stability. This review, while recapitulating
the early lessons, analyses recent work (including work from authors'
laboratory) involving these twin approaches for protein stabilization.
In the case of chemical modification, both surface hydrophilization and
enhancing surface hydrophobicity are reported to have enhanced protein
stability in different cases. For cross-linking, the nature, span, and
position of the cross-link are important factors in the stabilization
achieved. It is also pointed out that in the case of aqueous-organic
cosolvent mixtures, protein stability may depend upon the nature of the
organic solvents. In the case of polyphenol oxidase and trypsin (at
least), it is possible to choose "good" solvents on the basis
of the Polarity index of the solvent.
KEY WORDS: protein stability, chemical modification, chemical
cross-linking, amyloglucosidase, beta-galactosidase, glycogen
phosphorylase, glycoproteins, glyceraldehyde-3-phosphate dehydrogenase,
beta-glucosidase, catalase, acid phosphatase, lysozyme,
penicillin G acylase, polyphenol oxidase, RNase, trypsin, chymotrypsin